Todd H Driver1, Ronit Katz2, Joachim H Ix3, Jared W Magnani4, Carmen A Peralta5, Chirag R Parikh6, Linda Fried7, Anne B Newman8, Stephen B Kritchevsky9, Mark J Sarnak10, Michael G Shlipak11. 1. School of Medicine, University of California, San Francisco, CA. 2. Collaborative Health Studies Coordinating Center, University of Washington, Seattle, WA. 3. Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA; Division of Preventive Medicine, Department of Family and Preventive Medicine, University of California, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA. 4. Section of Cardiovascular Medicine, Boston University School of Medicine, Boston, MA. 5. Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA. 6. Section of Nephrology, Department of Medicine, Yale University, New Haven, CT; Program of Applied Translational Research, Yale University, New Haven, CT. 7. Renal Section, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA. 8. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA. 9. Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC. 10. Division of Nephrology, Tufts Medical Center, Boston, MA. 11. Department of Medicine, University of California, San Francisco, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA; Department of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA. Electronic address: michael.shlipak@ucsf.edu.
Abstract
BACKGROUND: Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. PREDICTORS: Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). OUTCOMES: Incident heart failure over a median follow-up of 12 years. RESULTS: Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). LIMITATIONS: Generalizability to other populations is uncertain. CONCLUSIONS: Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude. Published by Elsevier Inc.
BACKGROUND:Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. PREDICTORS: Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). OUTCOMES: Incident heart failure over a median follow-up of 12 years. RESULTS: Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). LIMITATIONS: Generalizability to other populations is uncertain. CONCLUSIONS: Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude. Published by Elsevier Inc.
Authors: Mark J Sarnak; Andrew S Levey; Anton C Schoolwerth; Josef Coresh; Bruce Culleton; L Lee Hamm; Peter A McCullough; Bertram L Kasiske; Ellie Kelepouris; Michael J Klag; Patrick Parfrey; Marc Pfeffer; Leopoldo Raij; David J Spinosa; Peter W Wilson Journal: Hypertension Date: 2003-11 Impact factor: 10.190
Authors: Jade S Hiramoto; Ronit Katz; Joachim H Ix; Christina Wassel; Nicolas Rodondi; B Gwen Windham; Tamara Harris; Annemarie Koster; Suzanne Satterfield; Anne Newman; Michael G Shlipak Journal: Vascular Date: 2013-05-13 Impact factor: 1.285
Authors: Chirag R Parikh; Alkesh Jani; Vyacheslav Y Melnikov; Sarah Faubel; Charles L Edelstein Journal: Am J Kidney Dis Date: 2004-03 Impact factor: 8.860
Authors: Sushrut S Waikar; Venkata Sabbisetti; Johan Ärnlöv; Axel C Carlsson; Josef Coresh; Harold I Feldman; Meredith C Foster; Gudeta D Fufaa; Johanna Helmersson-Karlqvist; Chi-Yuan Hsu; Paul L Kimmel; Anders Larsson; Yumin Liu; Lars Lind; Kathleen D Liu; Theodore E Mifflin; Robert G Nelson; Ulf Risérus; Ramachandran S Vasan; Dawei Xie; Xiaoming Zhang; Joseph V Bonventre Journal: Nephrol Dial Transplant Date: 2016-06-07 Impact factor: 5.992
Authors: Jonathan G Amatruda; Ronit Katz; Carmen A Peralta; Michelle M Estrella; Harini Sarathy; Linda F Fried; Anne B Newman; Chirag R Parikh; Joachim H Ix; Mark J Sarnak; Michael G Shlipak Journal: J Am Geriatr Soc Date: 2020-12-10 Impact factor: 5.562
Authors: Joachim H Ix; Ronit Katz; Nisha Bansal; Meredith Foster; Daniel E Weiner; Russell Tracy; Vasantha Jotwani; Jan Hughes-Austin; Dianne McKay; Francis Gabbai; Chi-Yuan Hsu; Andrew Bostom; Andrew S Levey; Michael G Shlipak Journal: Am J Kidney Dis Date: 2016-12-23 Impact factor: 8.860
Authors: Alexandra K Lee; Ronit Katz; Vasantha Jotwani; Pranav S Garimella; Walter T Ambrosius; Alfred K Cheung; Lisa H Gren; Javier A Neyra; Henry Punzi; Kalani L Raphael; Michael G Shlipak; Joachim H Ix Journal: Hypertension Date: 2019-08-05 Impact factor: 10.190
Authors: Ahmad Kaddourah; Stuart L Goldstein; Rajit Basu; Edwards J Nehus; Tara C Terrell; Lori Brunner; Michael R Bennett; Christopher Haffner; John L Jefferies Journal: Pediatr Nephrol Date: 2016-05-02 Impact factor: 3.714
Authors: Alexander R Opotowsky; Fernando R Baraona; Finnian R Mc Causland; Brittani Loukas; Elizabeth Landzberg; Michael J Landzberg; Venkata Sabbisetti; Sushrut S Waikar Journal: Heart Date: 2016-09-26 Impact factor: 5.994
Authors: Nisha Bansal; Myra A Carpenter; Daniel E Weiner; Andrew S Levey; Marc Pfeffer; John W Kusek; Jianwen Cai; Lawrence G Hunsicker; Meyeon Park; Michael Bennett; Kathleen D Liu; Chi-Yuan Hsu Journal: J Am Soc Nephrol Date: 2015-11-04 Impact factor: 10.121
Authors: Vasantha K Jotwani; Alexandra K Lee; Michelle M Estrella; Ronit Katz; Pranav S Garimella; Rakesh Malhotra; Dena E Rifkin; Walter Ambrosius; Barry I Freedman; Alfred K Cheung; Kalani L Raphael; Paul Drawz; Javier A Neyra; Suzanne Oparil; Henry Punzi; Michael G Shlipak; Joachim H Ix Journal: Am J Nephrol Date: 2019-04-02 Impact factor: 3.754